Ophthalmic fluid

ABSTRACT

An ophthalmic fluid containing at least one triglyceride, diglyceride, or monoglyceride which is chemically similar or compatible with compounds found naturally in the lipid layer of the tear film of an ocular substrate. Preferably the glycerides are derived from a fatty acid containing at least one unsaturated bond in a cis-configuration in the fatty acid residue. The ophthalmic fluid is arranged in use to provide a protective film across a tear film of an ocular substrate. Furthermore, the ophthalmic fluid is also arranged in use to provide a protective film intermediate a lipid layer of the tear film of the ocular substrate and a contact lens.

FIELD OF THE INVENTION

[0001] The present invention relates to an ophthalmic fluid forimproving wear comfort of contact lenses.

BACKGROUND OF THE INVENTION

[0002] The tear film, which is the interface between the externalenvironment and the ocular surface has several different functions. Itforms a smooth refractive surface over the otherwise irregular cornealsurface and lubricates the eyelids. Moreover, it maintains an optimalextracellular environment for epithelial cells of the cornea andconjunctiva where the electrolyte composition, osmolarity, pH, oxygenand carbon dioxide concentrations, nutrient and growth factorconcentrations are regulated within narrow limits.

[0003] Tears dilute and wash away noxious stimuli. They also provide anantibacterial system for the ocular surface and serve as an entrypathway for polymorphonuclear leukocytes in the case of injury to theocular surface. As tears have many and varied functions, it is notsurprising that they have a complex structure and are produced byseveral different sources.

[0004] The tear film consists of three layers. The inner layer is amucous layer that coats the cornea and conjunctiva. It was previouslythought to be 1 μm, but new evidence suggests that it may be farthicker. The mucous layer consists of mucins, electrolytes, water, IgA,enzymes, glycocalyx, microvilli, immunoglobins, and glycoproteins. Themiddle layer is an aqueous layer that is about 7 μm thick. This layercontains electrolytes, water, IgA, and proteins, many of which areantibacterial enzymes. Finally, the outer layer is a lipid layer about0.1 μm thick, which floats on the aqueous layer. The lipid layercontains a complex mixture of hydrocarbons, squalene, wax esters,cholesterol esters, triglycerides, diglycerides, monoglycerides, freefatty acids, free cholesterol, phospholipid, sterol esters, and polarlipids.

[0005] Each layer of the tear film is secreted by a different set oforbital glands.

[0006] The lipid layer is secreted primarily by the meibomian glandslocated in the tarsal plates of the lower and upper lids. The glands liein a row at the edge of the upper and lower eyelids and their ducts opendirectly onto the inner margin of the eyelids. There are approximately30 to 40 meibomian glands in the upper lid and 20 to 30 smaller glandsin the lower lid. Each gland has an orifice that opens on the lid marginbetween the tarsal “grey line” and the mucocutaneous junction. Thesebaceous glands of Zeis, located at the palpebral margin of the tarsus,and the aprocine glands of Moll, located at the roots of each eyelash,also secrete lipid that is incorporated into the tear film.

[0007] Sebum, also called meibum, the meibomian gland secretion,increases the surface tension of the tear film and decreases its rate ofevaporation. The evaporation rate of the normal tear film is low becauseof the protective lipid layer. Approximately 10% to 20% (0.085μL/minute) of the total tears secreted are lost by evaporation. In theabsence of the protective lipid layer, the rate of evaporation isincreased 10 to 20 times (1.7 μL/minute).

[0008] Meibomian gland secretions contribute to the formation of astable tear film. Meibomian gland dysfunction may result in dry eyesyndrome, keratoconjunctivitis and contact lens intolerance, presumablydue to an inadequate or a compromised tear film which is secondary tothe meibomian gland dysfunction itself. Meibomian gland dysfunction maybe often induced by soft contact lens wear, whilst mebomianitis mayresult from hard contact lens wear.

[0009] There are two major types of dry eye syndromes. Aqueous deficientdry eye syndrome is caused primarily from a lack of tear secretion fromthe lacrimal gland, whereas evaporative dry eye syndrome is typicallycaused by lipid insufficiency, a condition related to meibomian glanddysfunction. Both syndromes often co-exist.

[0010] It is thought that meibomian gland dysfunction may be caused inresponse to decreased androgen levels. Human lacrimal glands, meibomianglands and other ocular tissues have androgen receptors. The meibomiangland in particular appears to be a principal target site for androgenactivity on the ocular substrate. Androgens appear to stimulatemeibomian gland cells to produce lipids which maintains tear filmstability and prevent tear film evaporation. Decreased androgen levelsfrequently occur with fluctuating hormonal changes associated withmenopause, pregnancy, lactation and through the use of oralcontraceptives. It is also associated with the ageing process in men andwomen. Auto immune diseases such as Sjörgen's syndrome, rheumatoidarthritis, diabetes, thyroid abnormality, asthma, cataracts, glaucomaand lupus appear to correlate with the presence of meibomian glanddysfunction and evaporative dry eye syndrome.

[0011] Certain medications such as antidepressants, decongestants,diuretics, ulcer medication, tranquillisers and beta blockers can alsodecrease the body's ability to produce lubricating lipids.

[0012] Use of antiandrogen medications for prostatic hypertrophy orcancer also appear to correlate with the incidence of meibomian gladdysfunction and evaporative dry eye syndrome.

[0013] Evaporative dry eye syndrome may also be caused by environmentalconditions such as exposure to smoke, fluorescent lights, air pollution,wind, heaters, air conditioning and dry climates.

[0014] Similarly, behavioural patterns, particularly the tendency forVDU users to ignore the normal blinking process, may also interrupt tearproduction.

[0015] Contact lens wearers appear to be particularly susceptible toevaporative dry eye syndrome. Contemporary contact lenses are of twoprimary types: rigid gas permeable lenses (hard) and hydrogel lenses(soft) comprising between 30% to over 85% water of hydration. Rigid gaspermeable lenses are commonly formed from a co-polymer ofmethylmethacrylate and silicon, termed siloxaneacrylate.

[0016] The tear film thickness on the eye is reported to be up to 10microns, decreasing to 4.5 microns between blinks. The tear film isrelatively thin when compared with the thickness of any contact lens,which varies from a minimum of 30 microns to an average of 60-120microns, and over 250 microns for lenses of considerable optical power.Thus, the sheer mass of any contact lens may compromise the specificfunctions of the tear film which include the flushing action, theprevention of desiccation of the ocular tissue, the lubrication of theocular and palpebral surfaces, the formation of an optically smoothcurved surface, a vehicle for oxygen and carbon dioxide transport, andthe defence of the cornea against trauma, infection or disease. The roleof the lipid layer in preventing evaporation is relevant to contact lenswear. If the meibomian glands are obstructed, essentially eliminatingthe lipid layer, the rate of evaporation dramatically increases by afactor of 10 to 20.

[0017] The lipid layer on the surface of all contact lenses iscompromised as compared to the lipid layer of the cornea without thecontact lenses. A well-fitted contact lens has to rest on a continuousaqueous tear layer sandwiched between the lens and the epithelium, andit has to be coated with a continuous tear film complete with asuperficial lipid layer. However, all contemporary contact lenses areunable to mimic the ocular surface properties, and therefore acomparable tear film on the lens surfaces is unable to form.

[0018] A lipid layer does not form on hard lenses. There are conflictingreports regarding the presence and/or characteristics of the lipid layerforming on soft lenses. Some claim the complete absence of a lipidlayer, while others report it as present but thin, its depth beingdependent on the water content of the lens.

[0019] Clinical experience indicates that individuals without objectivesigns of dry eyes or subjective symptoms may experience classical dryeye symptoms while wearing contact lenses. When the contact lens isplaced on the eye, the lens alters the normal structure of the tear filmand affects its rate of evaporation. It is thought that the lipid layeris compromised causing dehydration of the aqueous layer to accelerateand tears to macerate the skin.

[0020] The present invention seeks to overcome at least some of theaforementioned disadvantages

SUMMARY OF THE INVENTION

[0021] In accordance with one aspect of the invention there is providedan ophthalmic fluid, wherein the ophthalmic fluid is arranged in use toprovide a protective film across a tear film of an ocular substrate, theophthalmic fluid comprising at least one glyceride of formula (I):

[0022] wherein R¹═R²═R³ is —O—CO—R; or R¹═R³ is O—CO—R when R² is OH, orR¹ is —O—CO—R when R²═R³═OH; R is a fatty acid residue containing atleast one unsaturated bond, and R is the same or different when R¹═R³ orR¹═R²═R^(3.)

DESCRIPTION OF THE INVENTION

[0023] The ophthalmic fluid of the present invention contains at leastone triglyceride, diglyceride, or monoglyceride of a fatty acidcontaining at least one unsaturated bond which is chemically similar tothose compounds found naturally in the lipid layer of the tear film ofthe eye. Alternatively, the ophthalmic fluid of the present inventioncontains at least one triglyceride, diglyceride, or monoglyceride of afatty acid containing at least one unsaturated bond which is compatiblewith those compounds found naturally in the lipid layer of the tear filmof the eye. Preferably, the ophthalmic fluid of the present inventioncontains a compound which biomimics at least one component of the lipidlayer of the tear film of the eye. It will also be understood that theophthalmic fluid may contain mixtures of the abovementioned components.Furthermore, it will also be understood that the fatty acid residuescomprised in the diglyceride or triglyceride may be the same ordifferent.

[0024] Preferably, the ophthalmic fluid contains at least onetriglyceride, diglyceride, or monoglyceride derived from a fatty acidcontaining at least one unsaturated bond in a cis-configuration in thefatty acid residue. However, glycerides derived from a fatty acidcontaining at least one unsaturated bond in a trans-configuration in thefatty acid residue may also be suitable. It is envisaged that the carbonchain length of the fatty acid residue will range from. 16 carbon to 20carbon atoms. However, the carbon chain length may vary from thatprovided that the melting point of the triglyceride, diglyceride ormonoglyceride is sufficiently low for handling and application purposes.Preferrably, the ophthalmic fluid contains at least one triglyceride,diglyceride or monoglyceride derived from oleic acid, linoleic acid,linolenic acid, palmitoleic acid, arachidonic acid, or mixtures thereof

[0025] While it is possible for the fatty acid of the glyceride offormula (I) to be administered alone, it is also possible to topicallyapply the glyceride of the present invention to the ocular substrate asa pharmaceutical composition. The pharmaceutical composition of thepresent invention comprises at least one glyceride, as defined above, inadmixture with one or more suitable carriers or diluents therefor andoptionally other therapeutic ingredients. The carrier(s) and diluent(s)must be “suitable” in the sense of being compatible with the othercomponents of the formulation and not deleterious to the recipientthereof.

[0026] Naturally occurring vegetable oils, such as grapeseed oil, havingglycerides derived from linoleic acid may also be used as an ophthalmicfluid in accordance with the present invention, particularly if thephysical properties of such an oil is to form oily droplets which willcoat the inner surface of the contact lens, and the chemical propertiesof the components of said oil are such as to be superficially recognisedby the ocular substrate as components of the lipid layer of the tearfilm of the eye.

[0027] Glycerides characteristically form oily droplets. Uponapplication of the ophthalmic fluid of the present invention to an innersurface of the contact lens, the glyceride molecules bond together toform a glyceride film which coats the inner surface of the contact lens.

[0028] The glyceride film has two purposes, one of which is to mask theforeign nature of the contact lens from the ocular substrate. Theglyceride film is comprised of glycerides which are chemically similarto those compounds found naturally in the lipid layer of the tear filmof the eye. In this way, the coated contact lens is superficiallyrecognised by the ocular substrate as a substance that is naturallyproduced by the eye. Irritation arising from rejection of an aliensubstance in the eye is subsequently reduced.

[0029] The purpose of the lipid layer of the tear film is to provide aneffective barrier against tear loss by dehydration and maceration. Whenthe lipid layer is compromised upon application of the contact lens tothe ocular substrate, the rate of evaporation from the tear filmincreases. The contact lens wearer consequently experiences discomfortand dry eye syndrome symptoms. The second purpose of the glyceride filmon the inner surface of the contact lens is thus to reinforce the lipidlayer of the tear film. The compromised lipid layer is effectivelyrebuilt or reinforced by the application of a glyceride film comprisedof substances which are naturally produced and secreted by the eye toform the lipid layer in the tear film.

[0030] The resulting reduction in tear loss and minimisation of lipidlayer disintegration is noticed by the eye as a reduction of theirritation usually associated with the application of contact lenses.Hence, the contact lens wearer experiences increased wear comfort.

[0031] The ophthalmic fluid of the present invention is suitable for usewith pas permeable (hard) contact lenses or hydrogel (soft) contactlenses. In use, 2-3 drops of the ophthalmic fluid of the presentinvention are placed onto the inside surface of the contact lens. Theophthalmic fluid is then distributed to cover fully and evenly theinside surface of the contact lens by rubbing the ophthalmic fluid intothe lens with a fingertip or any other suitable applicator. It isenvisaged that the ophthalmic fluid will be biologically sterile.

[0032] The lipid layer of the tear film is also compromised in subjectswho experience dry eye syndrome and meibomian gland dysfunction. Theophthalmic fluid of the present invention acts to reinforce the lipidlayer of the tear film because its components are either chemicallysimilar to, chemically and/or biologically compatible with, or biomimicat least one component naturally occurring in the lipid layer of thetear film. Thus the ophthalmic fluid of the present invention issuitable for the preparation of medicaments for the prevention andtreatment of dry eye syndrome. The ophthalmic fluid of the presentinvention is suitable for the preparation of medicaments for thetreatment of meibomian gland dysfuntion.

[0033] The present invention is further illustrated by the followingexamples.

[0034] The inside of a contact lens was coated with 2-3 drops of theophthalmic fluid of the present invention and fitted to the subject inthe conventional manner. The subject reported on the perceived ease ofinserting the coated lens, the subject's sensual reaction to the coatedlens and the resulting vision through the coated lens, in relation tohard and soft contact lenses.

EXAMPLE 1 Triolein(1,2,3-tri(cis-9-octadecenoyl)glycerol) (SigmaChemicals, 99%)

[0035] The subject reported that a gas permeable (hard) lens coated withtriolein was very comfortable to insert, the edges of the lens seeminglysmoothed out so as to reduce, but not totally eliminate, the normaldiscomfort associated when inserting a hard lens. Once inserted, thesubject could not feel the presence of the coated lens. The subject'svision through the coated lens was excessively and persistently blurred.Excess triglyceride did not drain into the lacrimal ducts, and had to bephysically removed.

[0036] The subject reported that a hydrogel (soft) lens coated withtriolein was very difficult to insert and did not noticeably amelioratethe normal discomfort associated when inserting a soft lens. Thesubject's vision through the coated lens was clear.

EXAMPLE 2 Trilinolein(1,2,3-tri(cis, cis-9,12octadecadienoyl)glycerol)(Sigma Chemicals, 99%)

[0037] The subject reported that a gas permeable (hard) lens coated withtrilinolein was very comfortable to insert. In comparison to a hard lenscoated with triolein, however, the sensation caused by the edges of thelens on the eye was not reduced to the same extent by a hard lens coatedin trilinolein. Once inserted, the subject could not feel the presenceof the coated lens. The subject initially experienced blurred visionwhich cleared after approximately 60 seconds. Excess triglyceridedrained into the lacrimal ducts, and a residue did not remain on the eyesurface or eyelid. The subject reported no tear expulsion.

[0038] The subject reported that a hydrogel (soft) lens coated withtrilinolein was easy to insert, and produced a noticeable ameliorationof the normal discomfort associated when inserting a soft lens. Onceinserted, the subject could not feel the presence of the coated lens.The subject's vision through the coated lens was immediately clear.Excess triglyceride drained into the lacrimal ducts, and a residue didnot remain on the eye surface or eyelid. The subject reported no tearexpulsion.

EXAMPLE 3 Tripalmitolein(1,2,3-tri(cis-9-hexadecenoyl)glycerol) (SigmaChemicals, 98%)

[0039] The subject reported that a gas permeable (hard) lens coated withtripalmitolein was very comfortable to insert. In comparison to a hardlens coated with triolein, however, the sensation caused by the edges ofthe lens on the eye was not reduced to the same extent by a hard lenscoated in tripalmitolein. Once inserted, the subject could not feel thepresence of the coated lens. The subject's vision through the coatedlens was excessively blurred. Excess tripalmitolein did not drain intothe lacrimal ducts, and had to be physically removed.

[0040] The subject reported that a hydrogel (soft) lens coated withtripalmitolein was very difficult to insert as the lens was moreadhesive to a finger coated with the fluid than to the actual ocularsubstrate. However, once the lens was inserted onto the eye, the subjectfound the soft lens coated with tripalmitolein to be comfortable. Thesubject's vision through the coated lens was blurred.

EXAMPLE 4 Trilinolenin(1,2,3-tri(cis, cis,cis-9,12,15octadecatrienoyl)glycerol) (Sigma Chemicals, 98)

[0041] The subject reported that although a gas permeable (hard) lenscoated with trilinolenin was easy to insert, the subject experiencedextreme irritation with increased tear production and maceration of theocular substrate. The subject's vision through the coated lens wasblurred.

[0042] The subject reported that a hydrogel (soft) lens coated withtrilinolenin was difficult to insert, the lens becoming quite greasy tohandle. However, once the soft lens coated with trilinolenin wasinserted onto the ocular substrate, the coated lens was comfortable towear. The subject initially experienced blurred vision which clearedafter 2 minutes.

EXAMPLE 5 Triarachidonin(1,2,3-tri(cis, cis, cis, cis,-5,8,11,14-eicosatetraenoyl)glycerol) (Sigma Chemicals, 98%)

[0043] The subject reported that a gas permeable (hard) lens coated withtriarachidonin was easy to insert with no residual greasy feel. Onceinserted, the coated lens was comfortable to wear. The subject did notexperience tear production or maceration. The subject's vision throughthe coated lens was excessively and persistently blurred. The subjectreported that a hydrogel (soft) lens coated with triarachidonin was easyto insert with no residual greasy feel. However, a soft lens coated withtriarachidonin did not produce any noticeable improvement in thewearer's comfort. The subject experienced increased tear production uponinsertion of the soft lens, but no maceration. The subject had clearvision.

[0044] The subject noticed that the soft lens became cloudy or frosty inappearance upon application of triarachidonin onto its surface.

EXAMPLE 6:

[0045] Safflower Oil (Melrose, organic unrefined, cold pressed).Composition: (per 100 g) Saturates Palmitic  7 g Stearic  2 gMonounsaturates Oleic 12 g Polyunsaturates Linoleic 78 g

[0046] The subject reported that a gas permeable (hard) lens coated withsafflower oil was difficult to insert with a distinct residual greasyfeel. The subject experienced a painful stinging sensation uponinsertion of the coated lens onto the ocular substrate combined withmaceration. The subject's vision through the coated lens was excessivelyand persistently blurred.

[0047] The subject reported that a hydrogel (soft) lens coated withsafflower oil was difficult to insert, the lens becoming quite greasy tohandle. The subject experienced a painful stinging sensation uponinsertion of the coated lens onto the ocular substrate. The subject'svision through the coated lens was blurred. The excess oil did not draininto the lacrimal ducts, and had to be physically removed

EXAMPLE 7:

[0048] Walnut Oil (Anglia Oils Ltd). Composition: Saturates Palmitic 8-11% Monounsaturates Oleic 15-18% Polyunsaturates Linoleic 51-62%Linolenic 10-19%

[0049] The subject reported that a gas permeable (hard) lens coated withwalnut oil was difficult to insert with a distinct residual greasy feel.The coated lens was comfortable to wear, the only discomfort arisingfrom the edges of the lens. The subject's vision through the coated lenswas persistently blurred.

[0050] The subject reported that a hydrogel (soft) lens coated withwalnut oil was difficult to insert, the lens becoming quite greasy tohandle. The subject experienced a painful persistent irritation uponinsertion of the coated lens onto the ocular substrate. The coated lensalso produced excessive tear production. The subject's vision throughthe coated lens was blurred. The excess oil did not drain into thelacrimal ducts, and had to be physically removed

EXAMPLE 8:

[0051] Canola Oil (Melrose, organic unrefined). Composition: (per 100 g)Saturates Palmitic  7.0 g Stearic  7.0 g Monounsaturates Undetermined64.0 g Polyunsaturates Linoleic 19.5 g Linolenic  9.5 g

[0052] The subject reported that a gas permeable (hard) lens coated withcanola oil was difficult to insert with a distinct residual greasy feel.The subject experienced extreme discomfort and irritation upon insertionof the coated lens onto the ocular substrate combined with macerationand excessive tear production. The subject's vision through the coatedlens was excessively and persistently blurred.

[0053] The subject reported that a hydrogel (soft) lens coated withcanola oil was difficult to insert, the lens becoming quite greasy tohandle. The subject experienced a painful stinging sensation uponinsertion of the coated lens onto the ocular substrate, combined withmaceration and excessive tear production. The subject's vision throughthe coated lens was blurred.

EXAMPLE 9:

[0054] Grapeseed Oil (Aurora). Composition: Saturates Undetermined  7-8%Monounsaturates trace Polyunsaturates Linoleic 72-75% Linolenic trace

[0055] The subject reported that a gas permeable (hard) lens coated withgrapeseed oil was easy to insert and comfortable to wear. The subjectnoticed slight discomfort associated with the edges of the lens on theeye which was not reduced to the same extent as with a hard lens coatedwith triolein. The subject initially experienced blurred vision whichcleared after approximately 30 seconds. An oily residue did not remainon the eye surface or eyelid. The subject reported no tear expulsion.

[0056] The subject reported that a hydropel (soft) lens coated withgrapeseed oil was easy to insert, and produced a noticeable ameliorationof the normal discomfort associated when inserting a soft lens. Onceinserted, the subject could not feel the presence of the coated lens.The subject's vision through the coated lens was initially blurred, butcleared after 30 seconds.

[0057] Excess grapeseed oil drained into the lacrimal ducts, and aresidue did not remain on the eve surface or eyelid. The subjectreported no tear expulsion or maceration. In light of the results ofExamples 1 to 9, it is envisaged than the ophthalmic fluid of thepresent invention may contain a glyceride derived from oleic acid incombination with a glyceride derived from linoleic acid. The glyceridederived from oleic acid imparts a character to the ophthalmic fluid inwhich the edges of a hard lens are seemingly smoothed out so as toreduce the normal discomfort associated when inserting a hard lens,whilst the glyceride derived from linoleic acid provides improved wearcomfort and clear vision through the lens.

[0058] Modifications and variations as would be apparent to a skilledaddressee are deemed to be within the scope of the present invention.

What is claimed is:
 1. A method of providing a protective film intermediate a lipid layer of a tear film of an ocular substrate and a contact lens, comprising topically applying an ophthalmic fluid to the contact lens before applying the contact lens to the ocular substrate, wherein the ophthalmic fluid comprises at least one glyceride of formula (I):

wherein R¹═R²═R³ is O—CO—R; or R¹═R³ is O—CO—R when R² is OH; or R¹ is O—CO—R when R²═R³═OH; R is a fatty acid residue comprising 16-20 carbon atoms and containing at least one unsaturated bond, and R is the same or different when R¹═R³ or R¹═R²═R³.
 2. The method according to claim 1, characterized in that irritation to the ocular substrate associated with the application of the contact lens to the ocular substrate is reduced.
 3. The method according to claim 1, characterized in that the method prevents and treats dry eye syndrome experienced by contact lens wearers.
 4. The method according to claim 1, characterized in that the method reinforces the lipid layer of the tear film of the ocular substrate upon application of the contact lens to the ocular substrate.
 5. The method according to claim 1, characterized in that the fatty acid residue contains at least one unsaturated bond in a cis-configuration.
 6. The method according to claim 1, characterized in that the ophthalmic fluid contains at least one triglyceride, diglyceride, or monoglyceride derived from oleic acid, linoleic acid, linolenic acid, palmitoleic acid, arachidonic acid, or mixtures thereof.
 7. A method of providing a protective film intermediate a lipid layer of a tear film of an ocular substrate and a contact lens, comprising topically applying an ophthalmic fluid to the contact lens before applying the contact lens to the ocular substrate, wherein the ophthalmic fluid consists essentially of at least one glyceride of formula (I):

wherein R¹═R²═R³ is O—CO—R; or R¹═R³ is O—CO—R when R² is OH; or R¹ is O—CO—R when R²═R ³═OH; R is a fatty acid residue comprising 16-20 carbon atoms and containing at least one unsaturated bond, and R is the same or different when R¹═R³ or R¹═R²═R³.
 8. The method according to claim 7, characterized in that irritation to the ocular substrate associated with the application of the contact lens to the ocular substrate is reduced.
 9. The method according to claim 7, characterized in that the method reinforces the lipid layer of the tear film of the ocular substrate upon application of the contact lens to the ocular substrate.
 10. The method according to claim 7, characterized in that the fatty acid residue contains at least one unsaturated bond in a cis-configuration.
 11. The method according to claim 7, characterized in that the ophthalmic fluid contains at least one triglyceride, diglyceride, or monoglyceride derived from oleic acid, linoleic acid, linolenic acid, palmitoleic acid, arachidonic acid, or mixtures thereof. 